Targeting the DNA Damage Response Pathways and Replication Stress in Colorectal Cancer.

ABSTRACT:

Purpose

Genomic instability is a hallmark of cancer and targeting DNA damage response (DDR) is emerging as a promising therapeutic strategy in different solid tumors. The effectiveness of targeting DDR in colorectal cancer has not been extensively explored.

Experimental design

We challenged 112 cell models recapitulating the genomic landscape of metastatic colorectal cancer with ATM, ATR, CHK1, WEE1, and DNA-PK inhibitors, in parallel with chemotherapeutic agents. We focused then on ATR inhibitors (ATRi) and, to identify putative biomarkers of response and resistance, we analyzed at multiple levels colorectal cancer models highly sensitive or resistant to these drugs.

Results

We found that around 30% of colorectal cancers, including those carrying KRAS and BRAF mutati

SUBMITTER: Durinikova E 

PROVIDER: S-EPMC9433963 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature